Ion Mobility based analysis methods separate and analyze ions under elevated pressure conditions (compared to mass spectrometers), based upon differences in the coefficient of mobility in gases. A Differential Mobility Spectrometer (DMS), like a traditional time-of flight ion mobility spectrometer (IMS), separates and analyzes ions based on the mobility characteristics of the ions, but provides orthogonal ion characterization. In IMS ion separation occurs on the basis of ion species cross section, in DMS ion separation occurs on the basis of the alpha parameter, which is related to the differences in the ion mobility coefficient in varying strengths of electric field. Ions are pulsed into an IMS and pass through a drift tube while being subjected to a constant electric field. As they pass through the drift region, ions may interact with drift gas molecules. These interactions are specific for each ion species of a sample, and depend from cross section of analyzed ion species leading to an ion separation based on more than just mass/charge ratio. Due to differences in collision cross sections different ion species have different drift velocity toward the detector plate, yielding different arrival (or drift) times.
In contrast, in the collision-free vacuum conditions of a Time of Flight Mass Spectrometer (ToF-MS), the ion's flight time through the MS flight tube is determined solely by the ion's mass-to-charge ratio (m/z).
A DMS is similar to an IMS in that the ions are separated in a drift gas at ambient pressure conditions. However, unlike an IMS, the DMS uses an asymmetric electric field waveform that is applied between at least two parallel electrodes through which the ions pass, in a continuous manner, swept along in the transport gas flow stream. Ion separation occurs under the effect of a strong asymmetric waveform RF electric field oriented perpendicular to the direction of the transport gas flow stream. The electric field waveform typically has a short time duration at a high field portion of the waveform and then a longer time at a low field duration at an opposite polarity. The duration of the high field and low field portions are applied such that the net voltage (average voltage for one full period) being applied to the DMS filter electrodes is zero. Under these conditions, ions with different field dependent mobility coefficients have different trajectories due to their alpha parameters.
In some circumstances, a DMS has been interfaced with a mass spectrometer (MS) to provide an orthogonal separation method to the MS. This combination which includes two orthogonal methods takes advantage of the atmospheric pressure, gas phase, and continuous ion separation capabilities of the DMS and enhanced analytical power of the DMS-MS system.
By interfacing a DMS with an MS, numerous areas of sample analysis, including proteomics, peptide/protein conformation, pharmacokinetic, and metabolism analysis have been enhanced. In addition to pharmaceutical and biotech applications, DMS-based analyzers have been used for trace level explosives detection and petroleum monitoring.
The resolution of a DMS device improves with the addition of a counter-current gas flow prior to the DMS mobility cell. Such a configuration is exemplified in FIG. 1. A curtain gas is established by placing a curtain plate prior to the inlet of the DMS and applying a DC potential (typically 500-1500 V) to propel ions across the gap between the curtain plate aperture and the DMS inlet. In addition this approach has been demonstrated to help provide effective ion desolvation prior to the mobility analyzer.
It has been found that ion losses mostly occur during the ion introduction in the DMS analytical gap. This is a result from the presence of fringing electric fields which result from the presence of superimposed separating (RF) and compensation (DC) electric fields in the analytical gap of the DMS. Additionally, it has also been found that the efficiency of ion introduction into a DMS cell can be affected by the absolute values of the applied separation and compensation voltages, which lead to changing the effective trajectories of ions that are distinguished by coefficient mobility, polarity, and electric field dependence (alpha parameters). In some devices, for example, in systems with narrow analytical gaps, this manifests itself as significantly reduced signal measured when used in transparent mode (where no asymmetric or compensation voltage is applied) and introduces discrimination in ion transmission between ions with high and low mobility coefficients.